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Abstract：
BACKGROUND: At present, a number of clinical trials have been carried out on GLP-1 receptor agonist liraglutide in the treatment of polycystic ovary syndrome (PCOS). However, the effect of liraglutide on follicle development and its specific mechanism are still unclear.
METHODS: RNA sequencing was used to explore the molecular characteristics of granulosa cells from patients with PCOS treated with liraglutide. The levels of C-X-C motif chemokine ligand 10 (CXCL10) in follicular fluid were detected by ELISA, the expression levels of ovulation related genes and inflammatory factor genes in follicles and granulosa cells were detected by qPCR and the protein levels of connexin 43 (Cx43), Janus Kinase 2 (JAK2) and phosphorylated JAK2 were detected by Western blot. The mouse ovarian follicles culture system in vitro was used to detect the status of follicle development and ovulation.
RESULTS: In the present study, we found that liraglutide inhibited the secretion of inflammatory factors in PCOS granulosa cells, among which CXCL10 was the most significant. In addition, CXCL10 was significantly higher in granulosa cells and follicular fluid in PCOS patients than in non-PCOS patients. We applied in vitro follicle culture and other techniques to carry out the mechanism exploration which revealed that CXCL10 disrupted the homeostasis of gap junction protein alpha 1 (GJA1) between oocyte and granulosa cells before physiological ovulation, thus inhibiting follicular development and ovulation. Liraglutide inhibited CXCL10 secretion in PCOS granulosa cells by inhibiting the JAK signaling pathway and can improved dehydroepiandrosterone (DHEA)-induced follicle development disorders, which is reversed by CXCL10 supplementation.
CONCLUSIONS: The present study suggests that liraglutide inhibits CXCL10 secretion in granulosa cells through JAK signaling pathway, thereby improving the homeostasis of GJA1 between oocyte and granulosa cells before physiological ovulation and ultimately improving the follicular development and ovulation of PCOS, which provides more supportive evidence for the clinical application of liraglutide in the treatment of ovulatory disorders in PCOS.
BACKGROUND: Not applicable.
METHODS: RNA sequencing was used to explore the molecular characteristics of granulosa cells from patients with PCOS treated with liraglutide. The levels of C-X-C motif chemokine ligand 10 (CXCL10) in follicular fluid were detected by ELISA, the expression levels of ovulation related genes and inflammatory factor genes in follicles and granulosa cells were detected by qPCR and the protein levels of connexin 43 (Cx43), Janus Kinase 2 (JAK2) and phosphorylated JAK2 were detected by Western blot. The mouse ovarian follicles culture system in vitro was used to detect the status of follicle development and ovulation.
RESULTS: In the present study, we found that liraglutide inhibited the secretion of inflammatory factors in PCOS granulosa cells, among which CXCL10 was the most significant. In addition, CXCL10 was significantly higher in granulosa cells and follicular fluid in PCOS patients than in non-PCOS patients. We applied in vitro follicle culture and other techniques to carry out the mechanism exploration which revealed that CXCL10 disrupted the homeostasis of gap junction protein alpha 1 (GJA1) between oocyte and granulosa cells before physiological ovulation, thus inhibiting follicular development and ovulation. Liraglutide inhibited CXCL10 secretion in PCOS granulosa cells by inhibiting the JAK signaling pathway and can improved dehydroepiandrosterone (DHEA)-induced follicle development disorders, which is reversed by CXCL10 supplementation.
CONCLUSIONS: The present study suggests that liraglutide inhibits CXCL10 secretion in granulosa cells through JAK signaling pathway, thereby improving the homeostasis of GJA1 between oocyte and granulosa cells before physiological ovulation and ultimately improving the follicular development and ovulation of PCOS, which provides more supportive evidence for the clinical application of liraglutide in the treatment of ovulatory disorders in PCOS.
BACKGROUND: Not applicable.
摘要：
背景：目前，已经对GLP-1受体激动剂利拉鲁肽治疗多囊卵巢综合征(PCOS)进行了多项临床试验.然而,利拉鲁肽对卵泡发育的影响及其具体机制尚不清楚。
方法：使用RNA测序来探索利拉鲁肽治疗的PCOS患者颗粒细胞的分子特征。ELISA法检测卵泡液中C-X-C基序趋化因子配体10(CXCL10)水平,qPCR检测卵泡和颗粒细胞中排卵相关基因和炎症因子基因的表达水平,Westernblot检测Janus激酶2(JAK2)和磷酸化JAK2。采用小鼠卵泡体外培养系统检测卵泡发育和排卵情况。
结果：在本研究中，我们发现利拉鲁肽抑制PCOS颗粒细胞炎症因子的分泌,其中CXCL10最为显著。此外,PCOS患者颗粒细胞和卵泡液中的CXCL10明显高于非PCOS患者。我们应用体外卵泡培养和其他技术进行了机制探索，揭示了CXCL10在生理排卵前破坏了卵母细胞和颗粒细胞之间的间隙连接蛋白α1（GJA1）的稳态，从而抑制卵泡发育和排卵。利拉鲁肽通过抑制JAK信号通路抑制PCOS颗粒细胞CXCL10的分泌，可改善脱氢表雄酮（DHEA）诱导的卵泡发育障碍，通过补充CXCL10可以逆转。
结论：本研究提示利拉鲁肽通过JAK信号通路抑制颗粒细胞中CXCL10的分泌，从而改善生理性排卵前卵母细胞和颗粒细胞之间GJA1的稳态，最终改善PCOS的卵泡发育和排卵，为临床应用利拉鲁肽治疗多囊卵巢综合征排卵障碍提供了更多的支持性证据。
背景：不适用。
方法：使用RNA测序来探索利拉鲁肽治疗的PCOS患者颗粒细胞的分子特征。ELISA法检测卵泡液中C-X-C基序趋化因子配体10(CXCL10)水平,qPCR检测卵泡和颗粒细胞中排卵相关基因和炎症因子基因的表达水平,Westernblot检测Janus激酶2(JAK2)和磷酸化JAK2。采用小鼠卵泡体外培养系统检测卵泡发育和排卵情况。
结果：在本研究中，我们发现利拉鲁肽抑制PCOS颗粒细胞炎症因子的分泌,其中CXCL10最为显著。此外,PCOS患者颗粒细胞和卵泡液中的CXCL10明显高于非PCOS患者。我们应用体外卵泡培养和其他技术进行了机制探索，揭示了CXCL10在生理排卵前破坏了卵母细胞和颗粒细胞之间的间隙连接蛋白α1（GJA1）的稳态，从而抑制卵泡发育和排卵。利拉鲁肽通过抑制JAK信号通路抑制PCOS颗粒细胞CXCL10的分泌，可改善脱氢表雄酮（DHEA）诱导的卵泡发育障碍，通过补充CXCL10可以逆转。
结论：本研究提示利拉鲁肽通过JAK信号通路抑制颗粒细胞中CXCL10的分泌，从而改善生理性排卵前卵母细胞和颗粒细胞之间GJA1的稳态，最终改善PCOS的卵泡发育和排卵，为临床应用利拉鲁肽治疗多囊卵巢综合征排卵障碍提供了更多的支持性证据。
背景：不适用。
